You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic. For video creation, please contact our Academic Video Service.
Version Summary Created by Modification Content Size Created at Operation
1 Ivana Škrlec + 1555 word(s) 1555 2022-01-06 09:24:34 |
2 format correct Vivi Li -75 word(s) 1480 2022-01-10 02:22:04 |

Video Upload Options

We provide professional Academic Video Service to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Škrlec, I. Circadian Clock Gene Polymorphisms and Metabolic Syndrome. Encyclopedia. Available online: https://encyclopedia.pub/entry/17906 (accessed on 13 December 2025).
Škrlec I. Circadian Clock Gene Polymorphisms and Metabolic Syndrome. Encyclopedia. Available at: https://encyclopedia.pub/entry/17906. Accessed December 13, 2025.
Škrlec, Ivana. "Circadian Clock Gene Polymorphisms and Metabolic Syndrome" Encyclopedia, https://encyclopedia.pub/entry/17906 (accessed December 13, 2025).
Škrlec, I. (2022, January 08). Circadian Clock Gene Polymorphisms and Metabolic Syndrome. In Encyclopedia. https://encyclopedia.pub/entry/17906
Škrlec, Ivana. "Circadian Clock Gene Polymorphisms and Metabolic Syndrome." Encyclopedia. Web. 08 January, 2022.
Circadian Clock Gene Polymorphisms and Metabolic Syndrome
Edit
This entry is adapted from the peer-reviewed paper 10.3390/biology11010020

Metabolic syndrome is a cluster of cardio-metabolic risk factors and comorbidities, including central obesity, hypertension, hyperglycemia, and dyslipidemia. In addition, different studies have shown that the disturbances in circadian rhythm are connected with components of metabolic syndrome. Circadian rhythm is the central regulator of every aspect of human health and metabolism, and metabolic homeostasis is essential in regulating energy metabolism, especially in adipose tissue. 

circadian clock genes hypertension metabolic syndrome type 2 diabetes mellitus obesity

1. Introduction

Metabolic syndrome (MetS) is a set of cardiometabolic disorders associated with cardiovascular risk factors [1][2]. Metabolic syndrome is a combination of at least three metabolic disorders that include elevated blood triglyceride levels, decreased HDL levels (high-density lipoprotein cholesterol), elevated fasting glucose levels, and high blood pressure [3]. MetS is thought to underlie obesity and insulin resistance, with central obesity involved in developing type 2 diabetes and cardiovascular diseases [2][4]. Due to a sedentary lifestyle, decreased physical activity and increased obesity remarkably contribute to type 2 diabetes development [2][3]. Moreover, sex, age, and lifestyle habits, such as drinking, tobacco smoking, and educational level could affect metabolic health regardless of obesity [5][6]. MetS negatively affects many body systems. Thus, insulin resistance causes microvascular damage leading to endothelial dysfunction and hypertension. Endothelial damage can cause atherosclerosis and hypertension, negatively affecting peripheral circulation and the heart and leading to kidney damage. In addition, MetS-associated dyslipidemia can trigger atherosclerosis that could lead to ischemic heart disease [3].
Circadian rhythm is a significant regulator of every aspect of human health and metabolism, and metabolic homeostasis is vital in regulating energy metabolism, especially in adipose tissue [4][7]. The central circadian clock is established in the hypothalamus’s suprachiasmatic nucleus (SCN) and determines diurnal rhythms [4][8]. The primary activators of transcription are CLOCK and BMAL1 proteins that heterodimerize each other, bind to enhancers, and rhythmically induce the transcription of other circadian clock genes. Period (PER) and cryptochrome (CRY) genes make up the negative feedback loop. Additionally, BMAL1 stimulates the expression of RORα and γ genes (RAR-orphan receptor). Casein kinases I δ and ε (CKI δ and ε), which degrade CRY and PER proteins, also contribute to the circadian activation of the clock gene. In addition to CRY and PER proteins, REV-ERB proteins (reverse erythroblastosis virus) prevent BMAL1 expression. Molecular clocks exist in all body cells and show 24 h periodicity [9][10][11].
A circadian metabolic disorder is a new risk factor for MetS. Many animal studies have investigated the relationship between circadian rhythm and metabolism. Circadian rhythm disorder has been associated with obesity, diabetes, hypertension, cardiovascular disease, and all components of MetS [4][12][13]. In addition, circadian rhythm disorders can lead to metabolic disorders, such as dyslipidemia, obesity, hyperglycemia, and hypertension [9][14][15].
Lipids and glucose have an essential role in developing MetS because they are an integral part of metabolic pathways. Circadian rhythm has a vital function in the homeostasis of lipid and glucose linked to obesity. Thus, it has a role in the risk of developing insulin sensitivity, diabetes, and cardiovascular diseases [4][16]. In addition, it has been shown that some of the core circadian rhythm genes are involved in maintaining lipid and glucose homeostasis, and circadian rhythm disorders may contribute to the development of metabolic health problems [10][17].
Many studies that have shown an association between circadian rhythm genes and metabolic syndrome have been conducted in animal models, most commonly in mice and rats that are nocturnal animals. The results of such research are applied to diurnal humans. However, there have been some inconsistencies among studies performed to date. Thus, Cho et al. showed that REV-ERBα alpha was associated with hyperglycemia and high triglyceride levels [18]. In contrast, Solt et al. showed that REV-ERBα alpha prevents weight gain by reducing fat mass [19].
Furthermore, the modern lifestyle contributes to reduced light exposure during the day (low indoor lighting levels) and increased light exposure at night, directly affecting our circadian rhythm and health, including the onset of metabolic syndrome. 

2. Discussion

CLOCK protein is included in the transcriptional control of circadian output genes and the core circadian clock. Hence, up to 10% of the human transcriptome may be under circadian regulation, and disorder in the CLOCK gene substantially influences transcription control.
The CLOCK rs1801260 (T3111C) polymorphism, placed in the 3′-UTR of the gene, has been extensively studied for its function in different MetS risk factors and in MetS patients on various diets. It is the first polymorphism recognized in the CLOCK gene to be linked with human MetS phenotypes [20]. However, although some studies observed a notable association between rs1801260 polymorphism and MetS susceptibility, the present meta-analysis did not find an association to overall MetS risk. That might happen due to the insufficient number of participants, the ethnic diversity of the studied population, and complex environmental circumstances that vary depending on the study [21]. However, insulin resistance is strongly associated with most risk factors related to MetS in all tested genetic models (allelic, dominant, and recessive). In contrast, hypertension as a sole risk factor is less likely to lead to MetS. Moreover, the importance of the rs1801260 polymorphism with MetS risk was observed in the Asian subgroup rather than in the Caucasian and Hispanic subgroups in stratified analysis. The C allele was an independent risk factor for potential insulin resistance in Asian patients with essential hypertension [22] and diabetes [23], while in Caucasian patients was positively associated with hypertension and coronary artery disease and negatively with obesity [24][25][26]. Monteleone et al. [12] noted that the rs1801260 genotypes were not linked with obesity. However, they observed a significant connection of the rs1801260 genotypes among overweight participants. Li et al. [15] observed that patients with the C allele incline towards insulin resistance and MetS, which could lead to the discrepancy. The rs1801260 polymorphism within 3′-UTR could be accountable for changes in the secondary structure of mRNA. Thus, polymorphism within 3′-UTR polymorphism results in various mRNA’s secondary structures that interfere with RNA-binding proteins and miRNA-182 binding sites in the 3′-UTR [27]. The CLOCK rs1801260 polymorphism might influence its transcription by modifying mRNA durability and then participating in MetS development. Ozburn et al. showed that rs1801260 polymorphism alters the expression, function, and stability of CLOCK mRNA and consequently affects the PER2 expression [28]. In conclusion, the abovementioned findings showed that BMAL1 rs7950226 polymorphism might be a predictive biomarker for MetS risk in the overall population. Nevertheless, additional molecular analyses require elucidation of all the assumptions regarding relevant mechanisms.
Unlike CLOCK rs1801260, rs6850524 polymorphism is an intron variant with three possible variations: C > G, C > A, and C > T, with C > G being the most common variant. Although studies revealed a discrepancy in the association of CLOCK rs6850524 polymorphism and MetS risk factors, this meta-analysis observed no association. However, some studies found an increased risk for hypertension [25] and obesity [29][30] associated with rs6850524. Still, additional studies are needed to investigate the molecular mechanism involved.
Similar to CLOCK rs6850524 polymorphism, BMAL1 rs7950226 polymorphism is an intron variant G > A and has been extensively studied for its function in different MetS risk factors. It has been revealed that carriers of the A allele or AA genotype have an elevated risk of developing MetS. Furthermore, Pappa et al. found that the A allele is significantly linked with a higher risk of gestational diabetes mellitus [31], while other studies showed an association with type 2 diabetes mellitus [32][33]. Moreover, rs7950226 GG genotype was associated with insulin resistance in patients with hypertension [22]. First, though, the molecular mechanisms underlying MetS need to be further clarified.
As observed in this study, CLOCK and BMAL1 gene polymorphisms are associated with some components of MetS. Polymorphisms within other circadian rhythm genes are also linked with elements of MetS. CRY1 and CRY2 polymorphisms showed a significant link between diabetes and obesity [34][32][30][35]. CRY1 polymorphisms are negatively associated with obesity [30]. Recent studies reported that PER2 and PER3 polymorphisms are associated with diabetes and obesity, metabolic syndrome components [32][36][37]. PER2 polymorphisms are negatively associated with diabetes, while PER3 polymorphisms are positively associated with obesity. Moreover, some studies observed a link between circadian gene REV-ERBα, REV-ERBβ, and RORα polymorphisms and obesity and diabetes [38][39][40]. RORα variants are linked with an increased possibility of developing diabetes [39], while PER3 and RORα polymorphisms increase the risk of MetS in the Taiwanese population [16]. However, those articles were not incorporated in the quantitative investigation due to a limited number of the same polymorphisms investigated. In addition, circadian rhythm genes might contribute to the risk of MetS independently and via gene-gene and gene-environment interplays. Additionally, to core clock genes, other genes expressed in a circadian manner and lifestyle could affect susceptibility to metabolic syndrome. For example, melatonin is a hormone responsible for regulating circadian rhythm and might affect glucose metabolism, associated with insulin resistance and T2DM and, therefore, MetS [41][42]. Moreover, genetic variants of melatonin receptor 1B (MTNR1B) might affect melatonin function and influence susceptibility to insulin resistance and diet-dependent weight loss [43][44]. Some studies suggest that genetic variants of core clock genes under a specific diet could influence risk factors for MetS, such as glucose levels, dyslipidemia, T2DM [45][46]. However, further similar research is required to be included in the meta-analysis to elucidate the precise link between the different circadian clock gene polymorphisms and the overall MetS risk.

References

  1. Zhang, H.; Shao, J.; Chen, D.; Zou, P.; Cui, N.; Tang, L.; Wang, D.; Ye, Z. Reporting and Methods in Developing Prognostic Prediction Models for Metabolic Syndrome: A Systematic Review and Critical Appraisal. Diabetes Metab. Syndr. Obes. Targets Ther. 2020, 13, 4981–4992.
  2. Regufe, V.M.G.; Pinto, C.M.C.B.; Perez, P.M.V.H.C. Metabolic syndrome in type 2 diabetic patients: A review of current evidence. Porto Biomed. J. 2020, 5, e101.
  3. Maury, E.; Ramsey, K.M.; Bass, J. Circadian Rhythms and Metabolic Syndrome. Circ. Res. 2010, 106, 447–462.
  4. Zimmet, P.; Alberti, K.G.M.M.; Stern, N.; Bilu, C.; El-Osta, A.; Einat, H.; Kronfeld-Schor, N. The Circadian Syndrome: Is the Metabolic Syndrome and much more! J. Intern. Med. 2019, 286, 181.
  5. Maugeri, A.; Hlinomaz, O.; Agodi, A.; Barchitta, M.; Kunzova, S.; Bauerova, H.; Sochor, O.; Medina-Inojosa, J.R.; Lopez-Jimenez, F.; Vinciguerra, M.; et al. Is Drinking Alcohol Really Linked to Cardiovascular Health? Evidence from the Kardiovize 2030 Project. Nutrients 2020, 12, 2848.
  6. Kunzova, S.; Maugeri, A.; Medina-Inojosa, J.; Lopez-Jimenez, F.; Vinciguerra, M.; Marques-Vidal, P. Determinants of Metabolic Health Across Body Mass Index Categories in Central Europe: A Comparison Between Swiss and Czech Populations. Front. Public Health 2020, 8, 108.
  7. Serin, Y.; Acar Tek, N. Effect of Circadian Rhythm on Metabolic Processes and the Regulation of Energy Balance. Ann. Nutr. Metab. 2019, 74, 322–330.
  8. Škrlec, I.; Milić, J.; Heffer, M.; Wagner, J.; Peterlin, B. Circadian clock genes and circadian phenotypes in patients with myocardial infarction. Adv. Med. Sci. 2019, 64, 224–229.
  9. Shimizu, I.; Yoshida, Y.; Minamino, T. A role for circadian clock in metabolic disease. Hypertens. Res. 2016, 39, 483–491.
  10. Kim, K.J. The Role of Circadian Clocks in Metabolism. Chronobiol. Med. 2019, 1, 107–110.
  11. Škrlec, I.; Milić, J.; Heffer, M.; Peterlin, B.; Wagner, J. Genetic variations in circadian rhythm genes and susceptibility for myocardial infarction. Genet. Mol. Biol. 2018, 41, 403–409.
  12. Valladares, M.; Obregón, A.; Chaput, J. Association between genetic variants of the clock gene and obesity and sleep duration. J. Physiol. Biochem. 2015, 71, 855–860.
  13. Škrlec, I.; Milić, J.; Cilenšek, I.; Petrovič, D.; Wagner, J.; Peterlin, B. Circadian clock genes and myocardial infarction in patients with type 2 diabetes mellitus. Gene 2019, 701, 98–103.
  14. Hernández-García, J.; Navas-Carrillo, D.; Orenes-Piñero, E. Alterations of circadian rhythms and their impact on obesity, metabolic syndrome and cardiovascular diseases. Crit. Rev. Food Sci. Nutr. 2019, 60, 1038–1047.
  15. Škrlec, I.; Milić, J.; Steiner, R. The Impact of the Circadian Genes CLOCK and ARNTL on Myocardial Infarction. J. Clin. Med. 2020, 9, 484.
  16. Lin, E.; Kuo, P.H.; Liu, Y.L.; Yang, A.C.; Kao, C.F.; Tsai, S.J. Effects of circadian clock genes and healthrelated behavior on metabolic syndrome in a Taiwanese population: Evidence from association and interaction analysis. PLoS ONE 2017, 12, e173861.
  17. Škrlec, I. Circadian rhythm and myocardial infarction. Med. Flum. 2019, 55, 32–42.
  18. Cho, H.; Zhao, X.; Hatori, M.; Yu, R.T.; Barish, G.D.; Lam, M.T.; Chong, L.W.; Ditacchio, L.; Atkins, A.R.; Glass, C.K.; et al. Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β. Nature 2012, 485, 123–127.
  19. Solt, L.; Wang, Y.; Banerjee, S.; Hughes, T.; Kojetin, D.; Lundasen, T.; Shin, Y.; Liu, J.; Cameron, M.; Noel, R.; et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature 2012, 485, 62–68.
  20. Zhang, L.; Ptáček, L.J.; Fu, Y.-H. Diversity of Human Clock Genotypes and Consequences. Prog. Mol. Biol. Transl. Sci. 2013, 119, 51.
  21. Yuan, H.P.; Sun, L.; Li, X.H.; Che, F.G.; Zhu, X.Q.; Yang, F.; Han, J.; Jia, C.Y.; Yang, Z. Association of Adiponectin Polymorphism with Metabolic Syndrome Risk and Adiponectin Level with Stroke Risk: A Meta-Analysis. Sci. Rep. 2016, 6, 31945.
  22. Li, G.Y.; Wang, H.; Chen, H. Association of insulin resistance with polymorphic variants of Clock and Bmal1 genes: A case–control study. Clin. Exp. Hypertens. 2020, 42, 371–375.
  23. Uemura, H.; Katsuura-Kamano, S.; Yamaguchi, M.; Arisawa, K.; Hamajima, N.; Hishida, A.; Kawai, S.; Oze, I.; Shinchi, K.; Takashima, N.; et al. Variant of the clock circadian regulator (CLOCK) gene and related haplotypes are associated with the prevalence of type 2 diabetes in the Japanese population. J. Diabetes 2016, 8, 667–676.
  24. Kolomeichuk, S.N.; Kurbatova, I.V.; Topchieva, L.V.; Korneva, V.A.; Poltorak, A.N.; Chambers, T.C.; Nemova, N.N. Association between CLOCK genetic variants and individual susceptibility to essential hypertension and coronary artery disease in Russian population. Exp. Clin. Cardiol. 2014, 20, 1798–1813.
  25. Salazar, P.; Konda, S.; Sridhar, A.; Arbieva, Z.; Daviglus, M.; Darbar, D.; Rehman, J. Common genetic variation in circadian clock genes are associated with cardiovascular risk factors in an African American and Hispanic/Latino cohort. IJC Hear. Vasc. 2021, 34, 100808.
  26. Gorokhova, S.G.; Generozov, E.V.; Yu, A.O.; Muraseeva, E.V.; Naumov, V.A.; Babikova, E.A.; Zaharczevskaya, N.B.; Prigorovskaya, T.S. Different association of CRY1 and CLOCK circadian genes with coronary atherosclerosis. J. Clin. Exp. Cardiol. 2014, 5, 2.
  27. Li, X.; Quon, G.; Lipshitz, H.D.; Morris, Q. Predicting in vivo binding sites of RNA-binding proteins using mRNA secondary structure. RNA 2010, 16, 1096.
  28. Ozburn, A.R.; Purohit, K.; Parekh, P.K.; Kaplan, G.N.; Falcon, E.; Mukherjee, S.; Cates, H.M.; McClung, C.A. Functional Implications of the CLOCK 3111T/C Single-Nucleotide Polymorphism. Front. Psychiatry 2016, 7, 67.
  29. Sookoian, S.; Gemma, C.; Gianotti, T.F.; Burgueño, A.; Castaño, G.; Pirola, C.J. Genetic variants of Clock transcription factor are associated with individual susceptibility to obesity. Am. J. Clin. Nutr. 2008, 87, 1606–1615.
  30. Ye, D.; Cai, S.; Jiang, X.; Ding, Y.; Chen, K.; Fan, C.; Jin, M. Associations of polymorphisms in circadian genes with abdominal obesity in Chinese adult population. Obes. Res. Clin. Pract. 2016, 10, S133–S141.
  31. Pappa, K.I.; Gazouli, M.; Anastasiou, E.; Iliodromiti, Z.; Antsaklis, A.; Anagnou, N.P. The major circadian pacemaker ARNT-like protein-1 (BMAL1) is associated with susceptibility to gestational diabetes mellitus. Diabetes Res. Clin. Pract. 2013, 99, 151–157.
  32. Kelly, M.A.; Rees, S.D.; Hydriem, Z.L.; Shera, A.S.; Bellary, S.; O’Hare, J.P.; Kumar, S.; Taheri, S.; Basit, A.; Barnett, A.H. Circadian gene variants and susceptibility to type 2 diabetes: A pilot study. PLoS ONE 2012, 7, e32670.
  33. Woon, P.Y.; Kaisaki, P.J.; Bragança, J.; Bihoreau, M.; Levy, J.C.; Farrall, M.; Gauguier, D. Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes. Proc. Natl. Acad. Sci. USA 2007, 104, 14412–14417.
  34. Hu, C.; Zhang, R.; Wang, C.; Wang, J.; Ma, X.; Hou, X.; Lu, J.; Yu, W.; Jiang, F.; Bao, Y.; et al. Variants from GIPR, TCF7L2, DGKB, MADD, CRY2, GLIS3, PROX1, SLC30A8 and IGF1 Are Associated with Glucose Metabolism in the Chinese. PLoS ONE 2010, 5, e15542.
  35. Kovanen, L.; Donner, K.; Kaunisto, M.; Partonen, T. CRY1, CRY2 and PRKCDBP genetic variants in metabolic syndrome. Hypertens. Res. 2015, 38, 186–192.
  36. Karthikeyan, R.; Marimuthu, G.; Sooriyakumar, M.; BaHammam, A.S.; Spence, D.W.; Pandi-Perumal, S.R.; Brown, G.M.; Cardinali, D.P. Per3 length polymorphism in patients with type 2 diabetes mellitus. Horm. Mol. Biol. Clin. Investig. 2014, 18, 145–149.
  37. de Azevedo, P.G.; Miranda, L.R.; Nicolau, E.S.; Alves, R.B.; Bicalho, M.A.C.; Couto, P.P.; Ramos, A.V.; de Souza, R.P.; Longhi, R.; Friedman, E.; et al. Genetic association of the PERIOD3 (PER3) Clock gene with extreme obesity. Obes. Res. Clin. Pract. 2021, 15, 334–338.
  38. Ruano, E.G.; Canivell, S.; Vieira, E. REV-ERB ALPHA polymorphism is associated with obesity in the Spanish obese male population. PLoS ONE 2014, 9, e104065.
  39. Zhang, Y.; Liu, Y.; Liu, Y.; Zhang, Y.; Su, Z. Genetic variants of retinoic acid receptor-related orphan receptor alpha determine susceptibility to type 2 diabetes mellitus in Han Chinese. Genes 2016, 7, 54.
  40. Tokat, B.; Kanca-Demirci, D.; Gul, N.; Satman, I.; Ozturk, O.; Ozder, A.; Kucukhuseyin, O.; Yilmaz-Aydogan, H. Determination of genetic changes of Rev-erb beta and Rev-erb alpha genes in Type 2 diabetes mellitus by next-generation sequencing. Gene 2020, 763, 145058.
  41. Shen, L.L.; Jin, Y. Effects of MTNR1B genetic variants on the risk of type 2 diabetes mellitus: A meta-analysis. Mol. Genet. Genomic Med. 2019, 7, e611.
  42. Patel, R.; Rathwa, N.; Palit, S.P.; Ramachandran, A.V.; Begum, R. Association of melatonin & MTNR1B variants with type 2 diabetes in Gujarat population. Biomed. Pharmacother. 2018, 103, 429–434.
  43. de Luis, D.A.; Izaola, O.; Primo, D.; Aller, R. A circadian rhythm-related MTNR1B genetic variant (rs10830963) modulate body weight change and insulin resistance after 9 months of a high protein/low carbohydrate vs a standard hypocaloric diet. J. Diabetes Complicat. 2020, 34, 107534.
  44. de Luis, D.A.; Izaola, O.; Primo, D.; Aller, R. Dietary-fat effect of the rs10830963 polymorphism in MTNR1B on insulin resistance in response to 3 months weight-loss diets. Endocrinol. Diabetes Nutr. 2020, 67, 43–52.
  45. Corella, D.; Asensio, E.M.; Coltell, O.; Sorlí, J.V.; Estruch, R.; Martínez-González, M.Á.; Salas-Salvadó, J.; Castañer, O.; Arós, F.; Lapetra, J.; et al. CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: Dietary modulation in the PREDIMED randomized trial. Cardiovasc. Diabetol. 2016, 15, 4.
  46. Gomez-Delgado, F.; Garcia-Rios, A.; Alcala-Diaz, J.F.; Rangel-Zuñiga, O.; Delgado-Lista, J.; Yubero-Serrano, E.M.; Lopez-Moreno, J.; Tinahones, F.J.; Ordovas, J.M.; Garaulet, M.; et al. Chronic consumption of a low-fat diet improves cardiometabolic risk factors according to the CLOCK gene in patients with coronary heart disease. Mol. Nutr. Food Res. 2015, 59, 2556–2564.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Biochemistry & Molecular Biology
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Ivana Škrlec
View Times: 743
Revisions: 2 times (View History)
Update Date: 10 Jan 2022
Table of Contents
    Notice
    You are not a member of the advisory board for this topic. If you want to update advisory board member profile, please contact office@encyclopedia.pub.
    OK
    Confirm
    Only members of the Encyclopedia advisory board for this topic are allowed to note entries. Would you like to become an advisory board member of the Encyclopedia?
    Yes
    No
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    There is no comment~
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    ${ selectedItem.replyTextCharacter }/${ selectedItem.replyMaxCharacter }
    Submit
    Cancel
    Confirm
    Are you sure to Delete?
    Yes No
    Academic Video Service
    Feedback